Dispensing device, dispensing method and method of detecting defective discharge of solution containing biological sample

Abstract

Proposed is dispensing technology capable of reliably spotting a biological sample on a solid phase. A head chip applies a voltage pulse between a diaphragm and separate electrodes based on a drive control signal output from a head driver IC, and discharges a solution containing protein filled in a pressurized chamber as a result of the elastic deformation of the diaphragm. A drive pulse generation circuit generates a drive voltage pulse and supplies this to the head chip in order to discharge a solution containing protein from the head chip. The drive current detection circuit detects a drive current flowing between the diaphragm and separate electrodes. Since the waveform of the detected drive current and the peak current value and so on differ in the case where the discharge status is normal and in the case where it is abnormal, a defective discharge can be discriminated by detecting such change.

1. A dispensing device, comprising:
 an electrode substrate having a plurality of separate electrodes formed in correspondence with each of a plurality of pressurized chambers to be filled with a solution containing a biological sample; 
 a pressurized chamber substrate disposed so as to face said electrode substrate in a minute gap, having a discharge mechanism for adjusting the pressure inside said pressurized chamber by mechanical displacement of an elastically deforming diaphragm with an electrostatic force corresponding to a potential difference with said separate electrodes, and discharging said solution from a nozzle hole; 
 a drive voltage generation circuit, connected between said diaphragm and said separate electrodes, for applying a drive voltage of a prescribed waveform between said diaphragm and said separate electrodes in order to discharge said solution from said nozzle hole; 
 a current detection circuit, which is connected between said diaphragm and said separate electrodes, configured to detect a current flowing between said diaphragm and separate electrodes during the period from the rising edge of the pulse of said drive voltage to the termination of discharge of the solution; and 
 discrimination means for comparing the detected current with a pre-stored normal current and for discriminating the existence of a defective discharge of the solution as a result of whether a peak waveform of a differential waveform of the current detected during the period with the current detection circuit appears on the positive side two consecutive times. 
 
     
     
       2. A dispensing device as in  claim 1 , wherein said current detection circuit detects said current during the period in which said diaphragm elastically deforms toward said separate electrodes or during the period in which said diaphragm elastically deforms away from said separate electrodes. 
     
     
       3. A dispensing device as in  claim 1 , wherein said discrimination means performs said discrimination by comparing said detected current with a pre-stored current to be employed upon a normal drive. 
     
     
       4. The dispensing device according to  claim 2 , wherein said discrimination means performs said discrimination by comparing said detected current with a pre-stored current to be employed upon a normal drive. 
     
     
       5. A dispensing device as in  claim 1 , further comprising recovery means for recovering the discharge mechanism which resulted in a defective discharge to a normal state. 
     
     
       6. The dispensing device according to  claim 5 , wherein said recovery means is suction means of a solution containing a biological sample. 
     
     
       7. A dispensing device as in of  claim 1 , wherein said biological sample is protein. 
     
     
       8. A dispensing device as in  claim 2 , wherein said biological sample is nucleic acid. 
     
     
       9. A method of detecting a defective discharge of a solution containing a biological sample in a discharge mechanism for adjusting the pressure inside said pressurized chamber by mechanical displacement of an elastically deforming diaphragm, which is disposed so as to face an electrode substrate in a minute gap having a plurality of separate electrodes formed in correspondence with each of the plurality of pressurized chambers to be filled with a solution containing a biological sample, with the electrostatic force corresponding to the potential difference with said separate electrodes, and discharging said solution from a nozzle hole, comprising the steps of:
 applying, under the control of a drive voltage generator circuit connected between said diaphragm and said separate electrodes, a drive voltage of a prescribed waveform between said diaphragm and said separate electrodes in order to discharge said solution from said nozzle hole; 
 detecting, under the control of a current detection circuit connected, separately from said drive voltage generation circuit, between said diaphragm and said separate electrodes, a current flowing between said diaphragm and separate electrodes during the period from the rising edge of the pulse of said drive voltage to the termination of discharge of the solution when said drive voltage is applied; and 
 discriminating the existence of a defective discharge of the solution based on whether a peak waveform of a differential waveform of the current detected during the period appears on the positive side two consecutive times. 
 
     
     
       10. A dispensing method, comprising the steps of:
 discriminating a defective discharge of a discharge mechanism with a method according to  claim 9  as a preparatory step for spotting a solution containing a biological sample on a substrate; and 
 selecting a discharge mechanism in which the discharge status is not defective and spotting said solution on the substrate. 
 
     
     
       11. The dispensing method according to  claim 10 , further comprising a step of preparing a microarray by spotting said solution containing a biological sample on an array. 
     
     
       12. The dispensing method according to  claim 10 , further comprising a step of preparing a protein chip by spotting said solution containing a biological sample on an array.